Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Totally Neoadjuvant FOLFOXIRI + Short-course Radiation + XELOX in Patients With Locally Advanced Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03484221
Recruitment Status : Recruiting
First Posted : March 30, 2018
Last Update Posted : August 7, 2018
Sponsor:
Information provided by (Responsible Party):
Jingdong Zhang, China Medical University, China

Brief Summary:
To evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation therapy and XELOX chemotherapy in the patients with locally advanced rectal cancer.

Condition or disease Intervention/treatment Phase
Rectal Neoplasms Drug Therapy Radiation Drug: FOLFOXIRI Radiation: Short-Course Radiation Therapy(5Gy*5) Drug: XELOX Phase 2

Detailed Description:

Neoadjuvant chemoradiation therapy with double cytotoxic agents is the standard treatment for the patients with locally advanced rectal cancer. Conventional treatment reduced the local recurrence but did not prolong the long-term survival. Furthermore, the patients with pathological complete response (pCR) did not benefit from double cytotoxic chemotherapy. Therefore, we chose triple cytotoxic agents FOLFOXIRI as the neoadjuvant chemotherapy. We will evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation and XELOX chemotherapy in the patients with locally advanced rectal cancer to achieve more pCR and longer survival.

In this prospective study, 30 patients with locally advanced rectal cancer will be recruited. Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by TME surgery. PET-CT examination will be performed before and after the 4 cycles of neoadjuvant FOLFOXIRI chemotherapy to assess the SUVmax changes. In addition, the dynamic changes of ctDNA in peripheral blood will be monitored at the PET-CT examination. In the course of treatment, safety evaluation will be carried out according to the standard of adverse reaction classification (CTCAE) 4.0.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Totally Neoadjuvant FOLFOXIRI Chemotherapy Followed by Short-course Radiation and XELOX Chemotherapy in Patients With Locally Advanced Rectal Cancer:an Open-label, Single-arm, Multicenter Phase II Study.
Actual Study Start Date : April 1, 2018
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2021

Arm Intervention/treatment
Experimental: FOLFOXIRI+short-course radiation+XELOX
Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by surgery.
Drug: FOLFOXIRI
IRINOTECAN 150 mg/m^2 IV over 1-h, day 1 + OXALIPLATIN 85 mg/m^2 IV over 2-h, day 1 + L-LEUCOVORIN 200 mg/m^2 IV over 2-h, day 1 + 5-FLUOROURACIL 2800 mg/m^2 IV 48-h continuous infusion, starting on day 1 administered every two weeks for 4 cycles (2 months).
Other Names:
  • Irinotecan
  • Oxaliplatin
  • 5-Fluorouracil

Radiation: Short-Course Radiation Therapy(5Gy*5)
Patients received a short-course radiation therapy(5Gy*5) after 4 cycles of FOLFOXIRI.

Drug: XELOX
OXALIPLATIN 130 mg/m^2 IV over 2-h, day 1 Capecitabine 1000 mg/m^2 twice daily days 1-14 every 3 weeks for 4 cycles.
Other Names:
  • Capecitabine
  • Oxaliplatin




Primary Outcome Measures :
  1. The ratio of tumor downstaging to stage 0 and stage I [ Time Frame: 2 years ]
    Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I


Secondary Outcome Measures :
  1. Tumor regression grade (TRG) [ Time Frame: 2 years ]
    The level of tumor regression under pathological examination

  2. Disease free survival [ Time Frame: 3 years ]
    Estimated from the date of surgery to the date of recurrence.

  3. Overall survival time [ Time Frame: 3 years ]
    Estimated from the date of enrollment to death from any cause.

  4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 3 years ]
    The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.

  5. ctDNA change [ Time Frame: 3 years ]
    The relationship between ctDNA and survival will be evaluated.

  6. SUVmax changes [ Time Frame: At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days) ]
    Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy

  7. Quality of life (QLQ C30) [ Time Frame: Every 2 weeks after the first treatment until 3 years ]
    Scores according to EORTC QLQ-C30 scoring manual



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 18-75 years old
  • Primary and pathological diagnosis of rectal adenocarcinoma
  • Radiographic evaluation of initial resectable rectal cancer
  • T staging was determined by MRI as T3N+ or T4Nx
  • Distal border of the tumor must be located < 12 cm from the anal verge
  • ECOG status: 0~1
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

Neutrophil count≥1.5×10^9/L Platelet count≥90×10^9/L Hemoglobin≥90g/L Total bilirubin (TBI) ≤ 1.5 * ULN Alanine aminotransferase (ALT)≤2.5 * ULN Aspartate aminotransferase (AST)≤2.5 * ULN Alkaline phosphatase (ALP)≤2.5 * ULN

- Signed informed consent; able to comply with study and/or follow- up procedures

Exclusion Criteria:

  • Previous treatment with oxaliplatin, irinotecan or fluorouracil
  • Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
  • Clear indication of involvement of the pelvic side walls by imaging
  • With distant metastasis
  • A history of malignant rectal cancer (i. e. sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer
  • Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia uncontrolled hypertension. Unexplained syncope occurred within 3 months
  • Digestive system diseases that would preclude study treatment or follow-up within the past 6 months
  • Gastric ulcers or duodenal ulcers for the treatment of resistance;
  • 3 or 4 grade gastrointestinal bleeding / bleeding;
  • Gastrointestinal perforation / fistula;
  • Abdominal abscess;
  • Infectious or inflammatory bowel disease
  • HIV infection and/or active hepatitis B virus infection
  • Pregnant or lactating women. Fertile patients must use effective contraception
  • Any serious acute or chronic disease that can not be involved in the study or to influence the interpretation of the results of the study
  • Other intervention clinical trials were combined at the same time.
  • Nerve or mental abnormality affecting cognitive ability
  • Other malignancy except effectively treated squamous cell or basal cell skin cancer,
  • Other situations that the researchers think should be excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03484221


Contacts
Layout table for location contacts
Contact: Yuanhe Wang, PhD 18900918794 zhangjd0228@hotmail.com

Locations
Layout table for location information
China
China Medical University Recruiting
Shenyang, China
Contact: Yuanhe Wang         
Sponsors and Collaborators
China Medical University, China
Investigators
Layout table for investigator information
Principal Investigator: Jingdong Zhang China Medical University, China

Layout table for additonal information
Responsible Party: Jingdong Zhang, Director, China Medical University, China
ClinicalTrials.gov Identifier: NCT03484221    
Other Study ID Numbers: LGIOG-2017-02
First Posted: March 30, 2018    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Irinotecan
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors